HIV is a sexually transmitted disease and a vaccine capable of preventing sexual transmission of HIV should elicit mucosal immune responses in the genital tract. The purpose of this project is to use the SIV/rhesus macaque system to define the best immunization strategy to elicit genital mucosal immune responses. Using a immunization protocol developed by dr. Lehner that specifically directs antigen to the genital lymph nodes; 3 female rhesus macaque were immunized with whole inactivated SIV in alum and 3 animals were immunized with SIVgp120 and SIVp27 in alum. The patterns of antigen specific cytokine secretion in CD4+ T cells was analyzed in the laboratory of Dr. Kiyono and all animals had TH1-like patterns of cytokine secretion after 1 inoculation. The pattern of cytokine secretion become TH2-like in 5 of 6 animals but remained TH1-like in 1 animal after boosting. The animals were challenged 14 days after the 2nd boost by intravaginal SIV inoculation. Four of 4 naive control animals became infected and 5 of 6 vaccinated animals became infected. The one immunized animal in which infectious virus could not be detected maintained a TH1-like pattern of cytokine secretion throughout the immunization protocol. A second project demonstrated that cynomologous macaques immunized rectally with recombinant poliovirus expressing HIV antigens (provided by Dr.Sandino and Feinberg) had HIV-specific immune responses in the serum and rectal washes.